1. Field of the Invention
This invention relates to novel 1-phenethylimidazoles substituted at the position .beta. to the imidazole ring by an optionally substituted hydrocarbyl carbonate or a mono-, di-, or trithiocarbonate, the use of these imidazoles as antimicrobial agents, the combination of these imidazoles with a suitable carrier, the preparation of these imidazoles, and the use of these imidazoles as intermediates in the preparation of 1-[.beta.-(R-thio)phenethyl]imidazoles.
This invention further relates to certain novel 1-phenethylimidazoles substituted at the position .beta. to the imidazole ring with a mercapto and the acid and base salts thereof, the preparation of these imidazoles, and the use of these imidazoles in the preparation of 1-[.beta.-(R-thio)phenethyl]imidazoles as well as other 1-phenethylimidazoles substituted at the position .beta. to the imidazole ring with a mono-, di- or trithiocarbonate or a thio-or dithioester.
2. Prior Art
It is generally known in the art that certain 1-(.beta.-aryl)ethylimidazole ethers and amines have anti-fungal and anti-bacterial activity. See, for example, U.S. Pat. Nos. 3,717,655 and 3,839,574, both to Godefroi and Heeres of Janssen and U.S. Pat. No. 3,658,813 to Godefroi and Schuermans of Janssen. Representative of the ethers is the compound miconazole nitrate having the formula ##STR1## the active ingredient in Monistat.RTM. Cream sold by Ortho Pharmaceutical Co. Such compounds are derived from 1-(.beta.-hydroxyphenethyl)imidazole or 1-(.beta.-aminophenethyl)imidazoles which are optionally substituted on the phenyl ring. (See Godefroi, et al, J. Med. Chem., 12, 784-91 (1969). Other 1-ethylimidazoles which are known include those disclosed in U.S. Pat. Nos. 3,796,704 and 3,892,764 both to Metzger et al of Bayer and U.S. Pat. No. 3,914,427 to Kramer et al of Bayer. These, too, show anti-fungal activity.
An entirely new class of 1-(.beta.-substituted phenethyl)imidazoles has now been discovered which shows very good anti-fungal and anti-bacterial activity. These are the 1-phenethylimidazoles which are substituted at the position .beta. to the imidazole with a carbonate or a mono-, di-, or trithiocarbonate. The existence of related compounds was hinted in the broad disclosure U.S. Pat. No. 3,796,704, but, unfortunately, no method was given for preparing such compounds.